The major route of elimination of epirubicin is the hepatobiliary system [see Clinical Pharmacology (12.3)]. Evaluate serum total bilirubin and AST levels before and during treatment with epirubicin hydrochloride injection. Patients with elevated bilirubin or AST may experience slower clearance of drug with an increase in overall toxicity. Lower doses are recommended in these patients [see Dosage and Administration (2.2)]. Patients with severe hepatic impairment have not been evaluated; therefore, do not use epirubicin hydrochloride injection in this patient population.
Assess serum creatinine before and during therapy. Dosage adjustment is necessary in patients with serum creatinine greater than 5 mg/dL [see Dosage and Administration (2.2)]. Patients undergoing dialysis have not been studied.
As with other cytotoxic agents, epirubicin hydrochloride injection may induce hyperuricemia as a consequence of the extensive purine catabolism that accompanies drug-induced rapid lysis of highly chemosensitive neoplastic cells (tumor-lysis syndrome). Other metabolic abnormalities may also occur. While not generally a problem in patients with breast cancer, consider the potential for tumor-lysis syndrome in potentially susceptible patients and consider monitoring serum uric acid, potassium, calcium, phosphate, and creatinine immediately after initial chemotherapy administration. Hydration, urine alkalinization, and prophylaxis with allopurinol to prevent hyperuricemia may minimize potential complications of tumor-lysis syndrome.
Administration of live or live-attenuated vaccines in patients immunocompromised by chemotherapeutic agents including epirubicin, may result in serious or fatal infections. Avoid vaccination with a live vaccine in patients receiving epirubicin hydrochloride injection. Killed or inactivated vaccines may be administered; however, the response to such vaccines may be diminished.
Epirubicin hydrochloride injection is emetigenic. Antiemetics may reduce nausea and vomiting; prophylactic use of antiemetics should be considered before administration of epirubicin hydrochloride injection, particularly when given in conjunction with other emetigenic drugs [see Adverse Reactions (6.2)].
As with other cytotoxic agents, thrombophlebitis and thromboembolic phenomena, including pulmonary embolism (in some cases fatal) have been coincidentally reported with the use of epirubicin hydrochloride injection.
Cimetidine increased the AUC of epirubicin by 50%. Stop Cimetidine treatment during treatment with epirubicin hydrochloride injection [see Clinical Pharmacology (12.3)].
Epirubicin hydrochloride injection can cause fetal harm when administered to a pregnant woman. Epirubicin was embryolethal and teratogenic in rats and rabbits. There are no adequate and well-controlled studies of epirubicin hydrochloride injection in pregnant women. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus. Women of child-bearing potential should be advised to avoid becoming pregnant during treatment and should use effective contraceptive methods [see Use In Specific Populations (8.1)].
Males with female sexual partners of childbearing potential should use contraception during and after cessation of epirubicin hydrochloride injection therapy. Epirubicin hydrochloride injection may damage testicular tissue and spermatozoa. Possible sperm DNA damage raises concerns about loss of fertility and genetic abnormalities in fetuses. The duration of this effect is uncertain [see Nonclinical Toxicology (13.1)].
Assess blood counts, including absolute neutrophil counts, and liver function before and during each cycle of therapy with epirubicin hydrochloride injection. Perform repeated evaluations of LVEF during therapy [see Warnings and Precautions (5.5 and 5.6)].
As with other anthracyclines, administration of epirubicin hydrochloride injection after previous radiation therapy may induce an inflammatory recall reaction at the site of the irradiation.
Because clinical trials are conducted under widely varying conditions, adverse reactions rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Integrated safety data are available from two studies (Studies MA-5 and GFEA-05) [see Clinical Studies (14.1)] evaluating epirubicin hydrochloride injection-containing combination regimens in patients with early breast cancer. Of the 1260 patients treated in these studies, 620 patients received the higher-dose epirubicin hydrochloride injection regimen (FEC-100/CEF-120), 280 patients received the lower-dose epirubicin hydrochloride injection regimen (FEC-50), and 360 patients received CMF. Serotonin-specific antiemetic therapy and colony-stimulating factors were not used in these trials. Clinically relevant acute adverse events are summarized in Table 1.
|Event||% of Patients|
|1 to 4||3/4||1 to 4||3/4||1 to 4||3/4|
|FEC & CEF = cyclophosphamide + epirubicin hydrochloride injection + fluorouracil; CMF = cyclophosphamide + methotrexate + fluorouracil; NA = not available Grade 1 or 2 changes in transaminase levels were observed but were more frequently seen with CMF than with CEF.|
|Body as a Whole|
Table 2 describes the incidence of delayed adverse events in patients participating in the MA-5 and GFEA-05 trials.
|% of Patients|
|*In study MA-5, cardiac function was not monitored after 5 years.|
|Asymptomatic drops in LVEF||2.1*||1.4||0.8*|
Two cases of acute lymphoid leukemia (ALL) were also observed in patients receiving epirubicin hydrochloride injection. However, an association between anthracyclines such as epirubicin hydrochloride injection and ALL has not been clearly established.
All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.